Pharmacokinetics (PK) describes what the body does to a drug substance—unlike pharmacodynamics (PD), which describes what the drug substance does to the body. PK comprises the four ADME processes: absorption, distribution, metabolism, and elimination.
Key pharmacokinetic parameters for practical work in clinical trials: AUC (area under the curve): a measure of the body’s total exposure to the active substance. Basis for bioequivalence comparisons. Cmax: maximum plasma concentration after a dose—relevant for safety assessments (toxicity). tmax: time at which Cmax is reached—dependent on route of administration and formulation.
Clearance (Cl): volume of plasma that is completely cleared of the active substance per unit time—a measure of elimination capacity. Volume of distribution (Vd): apparent distribution volume reflecting binding of the active substance to tissues and plasma. Half-life (t½): time for the plasma concentration to decrease by half—determines the dosing interval.
Linear vs non-linear (saturable) kinetics: In linear kinetics, clearance is concentration-independent (the more common case). In non-linear kinetics (e.g., phenytoin), enzyme systems become saturated, which makes dosing considerably more difficult. For CROs conducting Phase I trials and bioequivalence studies, correct PK sampling planning and analysis are key quality factors.